Chapter 20. Reactions of Singlet Oxygen with Nucleic Acids

Abstract

The chapter is aimed at providing an updated overview of the main available data on the oxidation of nucleic acids by singlet oxygen (1O2). Mechanistic insights into the selective oxidative pathways of guanine, the predominant DNA and RNA target, were gained from detailed model studies. These have also allowed identification of spiroiminodihydantoin and minor 8-oxo-7,8-dihydroguanine as the main decomposition products of nucleosides and nucleotides. Evidence has been provided that the latter guanine oxidation product and thionucleobases are also highly reactive to singlet oxygen. The 1O2 oxidation of isolated and cellular DNA and RNA is much more specific giving rise almost exclusively to 8-oxo-7,8-dihydroguanine though the intermediacy of 4,8-endoperoxide that subsequently rearranges into easily reducible 8-hydroperoxyguanine. It was also shown that 1O2 is not able to induce significant levels of strand breaks and/or alkali-labile sites in cellular DNA upon exposure to a chemical source of singlet oxygen. UVA irradiation of cells and human skin is able to oxidatively damage nuclear DNA as inferred from the measurement of 8-oxo-7,8-dihydroguanine. This has been rationalized in terms of the predominant implication of 1O2 produced by type-II photosensitization mechanism over Fenton-type reactions.